GENETIC MANIPULATIONS IN THE FRUIT FLY FIGHT CLUB: Aggression is a nearly universal feature of the behavior of social animals. In the wild, it is used for access to food and shelter, for protection from predation and for selection of mates, all of which are essential for survival. Despite its importance, little is known of the neural mechanisms that underlie aggressive behavior, other than that hormonal substances including amines, peptides and steroid hormones serve important roles in the behavior.

Our laboratory examines aggression using common strains of the fruit fly, Drosophila melanogaster. Although not widely known, male and female fruit flies do fight and males at least become territorial (establish dominance relationships). With the genome fully sequenced and with elegant methods available for the selective manipulation of genes in subsets of central nervous system neurons, behavioral studies of aggression in flies offer a powerful experimental system for identifying the fundamental mechanisms underlying this behavior. In our initial studies with this system, prior to the initiation of mutant studies, we carried out a quantitative analyses of fighting behavior in male and female flies (see labworks.hms.harvard.edu and PNAS 2002 and 2004).

Recent findings and current experimental studies include the following:

• We are using the GAL4/UAS system to alter amine neuron function in fly brains both while flies are fighting and during development. These studies are now at a single identified neuron level via the use of an intersectional genetics approach that allows us to reduce the populations of amine neurons identified using the GAL4 system alone. Details of the circuitry concerned with aggression are being worked out
• Learning and memory are associated with winning and losing fights in male flies. Losing flies develop a “loser mentality” in which they lose all subsequent fights despite fighting differently against familiar and non-familiar opponents. Recently we have extended the memory of the “loser mentality” to one week by having flies lose multiple fights. In addition we have generated “bullies” by inbreeding winners of fights for many generations. These flies lose all competitive advantage against all flies after a single loss to another bully. In collaborative studies, we have begun an examination of proteomic and genomic changes associated with these long-term effects.